On 1 November, Novartis reported the results of the Exceed trial, a Phase IIIb, double-blinded comparator trial of its interleukin (IL)-17 inhibitor, Cosentyx (secukinumab), against AbbVie ’s Humira (adalimumab) in patients with active psoriatic arthritis (PSA ).
Although Cosentyx showed numerically higher results for its primary endpoint of American College of Rheumatology (ACR ) 20 measured at Week 52, it failed to demonstrate statistically significant superiority over Humira. The safety profiles for each drug were consistent with those observed in previous studies. In its press release, Novartis noted that the data on the secondary endpoints, including the more rigorous ACR50 and Psoriasis Area and Severity Index (PASI) 90 are expected to be released at a future scientific conference. Although Cosentyx did not show statistical significance, GlobalData believes that a demonstration of joint improvement coupled with its established efficacy on the skin is still an encouraging result in the dynamic PsA market.
The results of the clinical trial have the potential to shift the perception of Cosentyx specifically and IL-17 inhibitors more generally. Key opinion leaders (KOLs) interviewed by GlobalData noted that within the PsA field, IL-17 inhibitors have a reputation for good skin clearance but have historically had less than optimal joint improvement compared to tumour necrosis factor (TNF) inhibitors for some patients. For this reason, although patients with extensive skin involvement may receive an IL-17 inhibitor as their first-line biologic, most patients will receive a TNF-inhibitor as first-line therapy to prevent further joint damage. Although not meeting superiority criteria is clearly not the optimal result for Novartis, these results also suggest that there is perhaps not as big a difference between the ultimate downstream effects of these different mechanisms of action as previously believed. The ability to demonstrate efficacy in all PsA disease domains remains an important differentiator in a saturated market, and Cosentyx appears to be an increasingly versatile option.
With these latest clinical trial results, Cosentyx appears to have solidified its foothold in the PsA space. In its Q3 financial report, Novartis cited the drug as a key growth driver for the company, and Cosentyx remains the highest-grossing IL-17 inhibitor in 2019 so far. However, this does not guarantee success for Cosentyx, since Humira is not AbbVie’s only contender in the market. AbbVie is currently awaiting the results of its active head-to-head, Select-PSA-1 trial of its Janus kinase (JAK-1) inhibitor, Rinvoq (upadacitinib), compared to Humira. Select-PsA1’s primary endpoint is also the ACR20, but it is also ambitiously measuring ACR70, which is an evaluation of how many subjects reach 70% improvement in joint symptoms. In the company’s recent quarterly earnings call, AbbVie said it expects Select-PSA-1 results to be available in H1 2020, and that it anticipates filing Rinvoq for PsA approval in 2021.
The impending launch of TNF-inhibitor biosimilars represents a major turning point in the PsA disease space and a potential opportunity for Cosentyx to capture additional patient share. The results of the Exceed trial strengthen the argument that Cosentyx is just as suitable for joint improvement as the TNF inhibitors, with even more effective skin clearance. However, Cosentyx will continue to face stiff competition in this dynamic market in the future.
GlobalData (2019) Psoriatic Arthritis: Global Drug Forecasts and Market Analysis to 2028, to be published